Phase II Forty-five patients with low-grade or transformed low-grade B-cell NHL were treated at 7 centers with Bexxar (Coulter Pharmaceutical), an iodine-131- labeled murine monoclonal antibody directed against the CD20 antigen on B cells. Patients received a single dosimetric dose (450 mg of unlabeled anti-B1 i.v. over 1 hour followed by 35 mg radiolabeled with 4 mCi I-131 over = hour) and then underwent periodic gamma camera scans and/or Nal probe counts over the next 7 days. Scan and/or probe data were used to calculate the required activity (mCi) of I-131 to deliver a desired therapeutic dose of radiation (cGy). This therapeutic dose was administered 7 to 14 days after the dosimetric dose and consisted of the same unlabeled and labeled antibody doses with the 35 mg dose labeled with enough I-141 to deliver a specified total body dose (a MTD determined in a prior phase I trial) of 65 cGy for patients with 100,000 - 149,999 platelets/mm3 and 75 cGy for patients with >=150,000. Patients had been heavily pretreated with chemotherapy prior to study entry: median prior different regimens = 4 (range, 1-8). All had failed an anthracyline or anthracenedione-containing regimen and had relapsed within 1 year after completion of their last chemotherapy regimen (as per protocol). Other characteristics included: mean age = 51, histology (low-grade 76%, transformed 24%) bulky disease 42%. Thirty-six patients received 75 cGy and 9 received 65 cGy total body dose: mean activity = 88 mCi (range 45-177). Twenty-seven of 45 (60%) patients responded (PR + CR) and 12/45 (27%) had a complete response (CR). The median duration of CR has not been reached (range 4.5 to 13.6+ months) with a median follow-up of ten months and 8/12 patients have ongoing CRs. Seven of 11 (64%) patients with transformed NHL responded and 5/11 (45%) had a CR. Twelve of 19 (63%) patients with bulky disease responded (13% CR). The principal toxicity was hematologic: ANC < 100/mm3 = 4% platelet count < 10,000/mm3 = 11%. The nadir typically occurred at week 5-6 with recovery by week 8-9. Transient mild to moderate non-hematologic toxicity was also observed with the most frequent events being fatigue, nausea, and fever. None of the 45 patients developed HAMA. These results in patients with poor prognostic factors indicate Bexxar to be a promising new agent for the treatment of low-grade and transformed low-grade NHL. Phase III Iodine-131 tositumomab is radiolabeled murine IgG2a monoclonal antibody directed against the CD20 antigen on B-cells. Sixty patients were enrolled at 8 sites in this phase III study designed to compare the efficacy outcomes between the patients' last chemotherapy therapy regimen and iodine-131 tositumomab. Thirty-six (60%) patients had low-grade NHL, 23 (38%) had transformed low-grade NHL, and 1 (2%) had intermediate grade NHL. Patients had to have received >= 2 prior chemotherapy regimens and had to have failed to respond to or progressed within 6 months of their last chemotherapy regimen. Baseline patient characteristics were: >60 years (45%), male (63%), median time from diagnosis (54 months), elevated LDH (46%), lymph node >= 5 cm. (54%), median number of prior chemotherapies (4). Patients received SSKI or Lugol's solution beginning >= 24 hours before the dosimetric dose and continuing for 14 days after the therapeutic dose. Patients received a single dosimetric dose (450 mg of antibody IV over 1 hour followed by 35 mg of antibody radiolabeled with 5 mCi of Iodine-131 over = hour) and then had a minimum of 3 whole body gamma camera counts obtained over the next 7 days. The gamma camera counts were used to calculate the required activity (mCi) to deliver the desired therapeutic dose (65 cGy which is the specific estimated whole body dose, for platelets 1000,001 - 149,999 and 75 cGy for platelets >=150,000). The single therapeutic dose (450 mg of unlabeled antibody IV over 1 hour followed by 35 mg of radiolabeled antibody over = hour) was administered 7-14 days after the dosimetric dose. An investigator-assessed response was observed in 17 of 60 (28%) patients following their last chemotherapy regimen compared to 40 of 60 (67%) patients following Iodine-131 tositumomab (p=0.000008; McNemar's test). A complete response was observed in 2 (3%) patients following their last chemotherapy regimen compared with 10(17%) following Iodine-131 tositumomab. Of the patients having nonequivalent duration of response (i.e., durations of response > 30 days different), 19% had a longer duration of response following their last chemotherapy regimen and 81% had a longer duration of response following Iodine-131 tositumomab (p=0.0002; McNemar's test). The response outcomes are currently undergoing review by a Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel; these results will be presented. The principal toxicity was hematologic; ANC< 100 = 2%, platelets < 10,000 = 2%. The nadir typically occurred at week 5-6 with recovery by week 8-9. Transient, mild to moderate nonhematologic toxicity also occurred with the most frequent events being fatigue, fever, and nausea. Three (5%) patients became HAMA positive following treatment. These results confirm earlier data and indicate that iodine-131 tositumomab is a safe and effective new agent for the treatment of low-grade and transformed low-grade NHL.